Potent Gastric Acid Inhibition Over 24 Hours by 4-Times Daily Dosing of Esomeprazole 20 mg

Abstract

Background: When administered at a standard dose, proton pump inhibitors (PPIs) do not always provide sufficient acid inhibition for all subjects, particularly in extensive metabolizers (EMs) of CYP2C19. Whether esomeprazole at a dose of 20 mg four times daily dosing (q.i.d.) can attain sufficient acid inhibition throughout 24 h in EMs remains unclear. We therefore investigated the efficacy of esomeprazole q.i.d. for acid inhibition. Methods: In a randomized cross-over design, 30 Helicobacter pylori-negative healthy young Japanese volunteers received esomeprazole at a dose of 20 mg two times a day (b.i.d.) or q.i.d. for 7 days. A pH monitoring was conducted before the trial as a control and on day 7 of both regimens. Results: Median pH values in the q.i.d. regimen were significantly higher than those with the b.i.d. regimen in EMs (b.i.d.: 5.3, q.i.d.: 6.6, p = 0.022), intermediate metabolizer (IM) (b.i.d.: 5.5, q.i.d.: 6.8, p = 0.005) and poor metabolizer (PM) (b.i.d.: 6.2, q.i.d.: 7.0, p = 0.047), respectively. Median pH with the b.i.d. regimen differed significantly by CYP2C19 genotypes (p = 0.004), but not the q.i.d. regimen (p = 0.384). Conclusion: Esomeprazole q.i.d. achieved potent acid inhibition in all Helicobacter pylori-negative subjects, irrespective of CYP2C19 genotype, which might be one of the rescue regimens for patients' refractory to PPI treatment.

Editorial: towards extended acid suppression - the search continues

“…These results are relevant since they have been obtained in CYP2C19 extensive metabolizers, the dominant genotype both in Japanese and Caucasian populations . The mean 24‐h intragastric pH was higher than, and the pH 4 holding time similar to, that recently reported after esomeprazole 20 mg q.d.s …”

“…12 The mean 24-h intragastric pH was higher than, and the pH 4 holding time similar to, that recently reported after esomeprazole 20 mg q.d.s. 13 When compared with standard doses of other PPIs, esomeprazole (40 mg once daily) provided more effective control of gastric acid in patients with symptomatic GERD. 14 Vonoprazan appears, therefore, superior to the best PPI currently available and displays a pharmacological profile with the potential to truly address the unmet clinical needs in GERD and other acid-related diseases.…”

A comparative study of 14‐day dual therapy (esomeprazole and amoxicillin four times daily) and triple plus bismuth therapy for first‐line Helicobacter pylori infection eradication: A randomized trial

“…When PPIs are administered four times daily, a stable and sufficient gastric acid suppression effect could be obtained, regardless of polymorphism. For example, the percentage of time with median intragastric pH was >6 or all‐day intragastric pH of ≥4 was >90% in subjects receiving rabeprazole (10 mg qid) or esomeprazole (20 mg qid) 27‐29 . Under these conditions, H pylori strains are in a state of active growth and reproduction and become more sensitive to amoxicillin 30,31 .…”

“…At present, only oral administration of rabeprazole and esomeprazole four times daily presents a sufficiently stable effect for gastric acid suppression. Related studies that report on the use of other types of PPIs, such as omeprazole, pantoprazole, and lansoprazole are still lacking 27,28 . Recently, Professor Graham has proposed the concept of relative potency for different PPIs, 34,35 that is, different PPIs can be used interchangeably according to their equivalent doses based on their relative potency in order to achieve a similar gastric acid suppression effect, and this remains to be confirmed with further studies.…”

Rapid metabolizer genotype of CYP2C19 is a risk factor of being refractory to proton pump inhibitor therapy for reflux esophagitis

“…13 Administration of 10-mg rabeprazole, 30-mg lansoprazole, and 10-mg esomeprazole four times daily in CYP2C19 RMs achieves sufficient inhibition of acid secretion. [51][52][53][54] Therefore, four times daily dosing of PPIs achieves potent acid inhibition, including overnight, suggesting potential utility as a regimen for patients who are refractory to standard once-daily PPI treatment.…”